The Tuberculosis Prevention Trial in progress in the Chingelput District in south India (Chingelput Trial) is providing an extensive data base for answering questions of major importance about the pathogenesis and epidemiology of tuberculosis as it exists today in a rural tropical area in a developing country. Thus far, the Chingelput Trial has revealed two major and unexpected findings: (1) the absence of a protective effect of BCG, (2) the number of Chingelput patients undergoing an early progression from infection to disease was only 10% of that observed in similar active case finding studies in other areas of the world. Another unique observation about tuberculosis in south India, made 20 years earlier and of potential relevance to the Chingelput Trial, was that 70% of isolates of tubercle bacilli from patients in MadrAS were of low virulence for guinea pigs. In preliminary studies of the virulence of Chingelput isolates in aerosol infected guinea pigs, we demonstrated a significant reduction in the extent of hematogenous spread to lung and spleen. We propose to utilize the Chingelput Data Bank, a research resource of international importance, to answer the question, "Does the tendency for hematogenous spread in aerosol infected guinea pigs have predictive value for the occurrence of hematogenous forms of tuberculosis in Chingelput patients. Isolates to be studied for their ability to spread hematogenously in aerosol infected guinea pigs include those recovered from urine, bone, or cerebrospinal fluid." If tubercle bacilli obtained from Chingelput patients do exhibit a reduced tendency to spread via the blood in guinea pigs and if this is reflected in a reduced frequency of hematogenous forms of tuberculosis in such patients, these data would provide the first laboratory evidence obtained on a large number of patients supporting a role for exogenous reinfection tuberculosis. If exogenous reinfection is shown to be a significant factor in the pathogenesis and epidemiology of tuberculosis in the Chingelput district, it not only explains both of the major unexpected Chingelput Trial observations, it also has important implications for the tuberculosis control strategy to be stressed in Chingelput and in other areas where similar circumstances exist.